Abstract
Solid pseudopapillary neoplasm (SPN) is a rare malignant tumour accounting for 0.1% to 2.7% of all pancreatic neoplasms and affecting young women. Peritoneal carcinomatosis (PC) is even rarer, with only 11 reported cases. We describe a twelfth case occurring 13 years after the resection of an SPN which ruptured peroperatively. This 35-year-old woman had first undergone complete cytoreductive surgery (CCRS) alone and disease had relapsed within 8 months. Ultimately, further CCRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and irinotecan. The patient is now alive and disease free 31 months after her last operation. In the literature, the surgical treatment of PC from an SPN has yielded disappointing results, with a 58% recurrence rate at intervals ranging from 1 to 19 years. As none of these patients developed distant metastases, indicating a strictly peritoneal disease, HIPEC might be a solution for preventing such recurrences.
- Cancer
- solid pseudopapillary neoplasm
- Frantz's tumour
- peritoneal carcinomatosis
- hyperthermic intraperitoneal chemotherapy
- cytoreductive surgery
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare malignant tumour of the pancreas, accounting for 0.13% to 2.7% of all pancreatic tumours (1-4) and by the year 2005, only 718 cases had been reported (5). In 1959, Frantz was the first to histologically describe this entity (6). It affects women in 83 to 96% of cases (sex ratio of 8.25 to 9.78/1), and is predominantly diagnosed between the age of 30 and 40 (5, 7-9). Eighty-five to 90% of lesions are diagnosed at an early stage and metastases occur in 10 to 15% of patients. Only 11 cases of peritoneal carcinomatosis (PC) from SPN have been so far reported in the literature (7, 10-19). We, here, report a twelfth case and discuss its management.
Case Report
A 35-year-old woman was admitted to a general hospital for lower abdominal pain. Her medical history included a distal splenopancreatectomy for a benign somatostinoma at the age of 22 years, multiple sclerosis and a smoking habit. A multiloculated pelvic mass was depicted on the CT scan (Figure 1). The chest CT scan and tumour markers were negative. The patient was scheduled for surgery. The peroperative exploration showed diffuse PC associated with a massively invaded right ovary. The surgeon performed peritoneal biopsies and resected the right ovary which was suspected to be responsible for the pain. The pathological diagnosis was a low-grade ovarian sarcoma and the patient was referred to our tertiary care centre. She had no signs of extraperitoneal disease and was scheduled for complete cytoreductive surgery (CCRS). This surgery required multiple peritoneal resections, a rectal resection, a hysterectomy and an omentectomy. Surprisingly, the pathological diagnosis was a massive peritoneal carcinomatosis arising from a solid pseudopapillary neoplasm of the pancreas (SPN). Histological samples of the distal splenopancreatectomy performed 13 years earlier in a third hospital were reviewed and confirmed the diagnosis of SPN with signs of malignancy (i.e. venous invasion, diffuse growth pattern, significant nuclear atypia), while the diagnosis of somatostinoma was ruled out. A retrospective analysis showed a tumour rupture had occurred during the initial pancreatic surgery. No adjuvant chemotherapy was administered and a radiological follow-up was planned. On the first abdominal CT scan 8 months after this third operation, 4 nodules were observed under the left diaphragm (Figure 2). A biopsy under endoscopic ultrasound confirmed the second peritoneal recurrence from an SPN. The patient was scheduled for a fourth surgical procedure. The peroperative work-up showed diffuse peritoneal disease with tumour nodules on the bladder, on the promontory, on the anterior aspect of the rectum, on both sides of the diaphragm and on the liver (Figure 3). CCRS required multiple peritoneal resections, a partial resection of the rectum and was combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and irinotecan at a temperature of 43°C for 30 min. No adjuvant chemotherapy was administered. The patient is now alive and disease free 31 months after CCRS plus HIPEC.
Multiloculated pelvic mass on the comptuted tomographic scan.
Discussion
This case report shows that SPN can give rise to extensive peritoneal seeding with a high recurrence rate, requiring four operations over a 15-year period for our patient. This disease was probably ultimately controlled with CCRS plus HIPEC. Peritoneal carcinomatosis in SPN is very rare, with only 11 cases reported in the literature (7, 10-19). All cases in the literature described a history of tumour spillage, when such information was mentioned, during the first surgical procedure, as observed in our patient (Table I). This strongly highlights the importance of operative care to obviate this type of recurrence. Once tumour spillage occurs, recurrences arise after a longer interval than in other cancer types (13 years in our patient; 1 to 19 years in the literature) (7, 11, 13-5, 17, 19). This interval should be acknowledged so that follow-up is prolonged in comparison with that applied for other types of cancer.
Nodules under the left diaphragm on the comptuted tomographic scan.
The first pitfall in this case was the initial pathological misdiagnosis after surgery of the pancreatic tail. Although rare, SPN should always be considered among the pancreatic tumours affecting young women (5, 7-9). Imaging can be confounding but a cystic component is present in 73% of cases (9). Pancreatic tumour markers [carbohydrate antigen 19-9, carcinoembryonic antigen (ACE), chromogranin A, endocrine pancreatic enzymes] are not overexpressed in this type of tumour (7-9). The final diagnosis of SPN requires specific immunohistochemical analyses. SPNs are mostly positive for CD10 and progesterone, they overexpress nuclear and cytoplasmic B-catenin, with a variable expression of synaptophysin and Neuron Specific Enolase (NSE) and are associated with loss or cytoplasmic migration of cadherin expression (20-23). The absence of chromogranin expression and, more recently, the identification of variation in the expression pattern of claudins, helps differentiate SPN from the main potential differential diagnoses which are endocrine tumours, pancreatoblastoma and acinar tumours (24). In our patient, the diagnosis should have been made at the first surgery; the strategy would have probably been the same as surgery remains the treatment of choice for SPN.
The second pitfall in this case was the tumour rupture during the initial pancreatic surgery. As the tumour biology is favourable, surgery yields very good long-term results with 5-year overall survival ranging from 93.4% to 100%, even in cases of locally advanced and metastatic disease (5, 8,23). Nevertheless, locoregional recurrence, estimated at between 2 and 7% in major series, occurred in 100% of the cases after an incomplete resection or tumour rupture (7-8, 25-26). In a recent study of 41 patients with SPN, all patients who underwent an R2 resection ultimately died of their disease after 37 months of follow-up (9). Preoperative treatments have been used successfully to shrink the tumour and avoid this spillage. One team reported a reduction in the tumour size from 15 cm to 3.5 cm after 6 months of 5fluorouracil/cisplatin in an SPN, initially invading the mesenteric vein, which was ultimately resected (27). Another team reported response of an initially locally advanced SPN after four cycles of cisplatin, ifosfamide, etoposide, and vincristine, which enabled a complete resection (28). In our opinion, this properative chemotherapy is the best option for locally advanced tumours in which complete resection may be jeopardised.
Peroperative view of the diffuse peritoneal carcinomatosis.
Reported cases of peritoneal carcinomatosis arising from solid pseudopapillay neoplasm of the pancreas in the literature.
Concerning the treatment of the peritoneal carcinomatosis from SPN, surgery alone has yielded disappointing results, with a 58% (7/12) peritoneal recurrence rate (7, 10-19). This is probably an underestimation of the real rate because follow-up in some of these patients was relatively short compared to the natural history of SPN. According to the literature, recurrences occur after a mean interval of 6.7 years and fewer than half of the reported cases had already reached this endpoint (7, 11, 14-15). Although this rate is very high, none of these patients developed distant metastases, indicating that the disease was confined to the peritoneum (7, 10-19). Considering our good results in rare tumours of the peritoneum (pseudomyxoma peritonei, malignant mesothelioma) and because this patient had an early recurrence after CCRS, performed in an experienced centre, we decided to add HIPEC to the fourth surgical intervention, although there are no data in the literature to support this approach (29-30). After a 31-month follow-up, this option seemed to be beneficial as no recurrence has to date been detected on imaging (third imaging follow-up examination). Based on the literature results, we plan to extend the length of surveillance to at least 10 years.
Conclusion
Iatrogenic rupture of an SPN of the pancreas is a major risk factor for peritoneal carcinomatosis which can occur up to 19 years later. When treating peritoneal carcinomatosis, surgery alone yields disappointing results with a 58% recurrence rate. Complete cytoreductive surgery combined with HIPEC might be more efficient.
Acknowledgements
The Authors thank Lorna Saint Ange for editing.
- Received December 23, 2011.
- Revision received January 31, 2012.
- Accepted February 2, 2012.
- Copyright© 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
References
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